Variants inHSD11B1gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes
- 1 January 2021
- journal article
- research article
- Published by Wiley in Diabetes/Metabolism Research and Reviews
- Vol. 37 (1), e3352
- https://doi.org/10.1002/dmrr.3352
Abstract
Background and aim 11 beta-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association ofHSD11B1SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. Materials and methods Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). Results The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96;P= .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37;P= .028). A follow-up study revealed that 29% of the individuals lost >= 5 mL min(-1)x 1.73 m(2)per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89;P= .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42;P= .004). Conclusion SNPs in theHSD11B1gene may confer susceptibility to DKD and to IR in T1D individuals.Funding Information
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance code 001)
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2016/15603‐0)
This publication has 38 references indexed in Scilit:
- Gender-dependent association of HSD11B1 single nucleotide polymorphisms with glucose and HDL-C levelsGenetics and Molecular Biology, 2014
- 11 beta-HYDROXYSTEROID DEHYDROGENASES: INTRACELLULAR GATE-KEEPERS OF TISSUE GLUCOCORTICOID ACTIONPhysiological Reviews, 2013
- Nocturnal activity of 11β-hydroxy steroid dehydrogenase type 1 is increased in type 1 diabetic childrenDiabetes & Metabolism, 2012
- Association between 11β-hydroxysteroid dehydrogenase type 1 gene polymorphisms and metabolic syndromeBiochemia Medica, 2012
- Association Study of Candidate Gene Polymorphisms and Obesity in a Young Mexican-American Population from South TexasArchives of Medical Research, 2011
- A combination of polymorphisms in HSD11B1 associates with in vivo 11β-HSD1 activity and metabolic syndrome in women with and without polycystic ovary syndromeActa Endocrinologica, 2011
- Evaluation of Hepatic 11 β-Hydroxysteroid Dehydrogenase Activity by Cortisone Acetate Test in Young Adults With Diabetes Mellitus Type 1Physiological Research, 2011
- Targeting the pre-receptor metabolism of cortisol as a novel therapy in obesity and diabetesThe Journal of Steroid Biochemistry and Molecular Biology, 2010
- 11?-Hydroxysteroid dehydrogenase Type 1: genetic polymorphisms are associated with Type 2 diabetes in Pima Indians independently of obesity and expression in adipocyte and muscleDiabetologia, 2004
- Cortisol metabolism and the role of 11β-hydroxysteroid dehydrogenaseBest Practice & Research Clinical Endocrinology & Metabolism, 2001